Background Stress-induced hyperglycemia (SIH) frequently occurs after liver transplantation, leading to impaired graft recovery and increased morbidity. This study aimed to identify independent intraoperative predictors of SIH and establish a simplified predictive model for early clinical application in non-diabetic transplant recipients. Methods Clinical data from 56 non-diabetic patients undergoing first-time liver transplantation (December 2019–November 2023) were retrospectively analyzed. Logistic regression identified independent predictors of postoperative SIH. A predictive model was developed, validated via receiver operating characteristic (ROC) curve analysis, and visualized with a clinical nomogram. Results The incidence of SIH was 46.4%. Multivariate analysis identified donor age (OR = 1.06, P = 0.033), anhepatic phase duration (OR = 1.16, P = 0.018), and pre-incision blood glucose (OR = 3.41, P = 0.009) as independent SIH predictors. The combined predictive model showed strong discriminative ability (AUC = 0.922; sensitivity = 84.6%, specificity = 90.0%), surpassing individual predictors. A nomogram was developed for rapid clinical risk assessment. Conclusions Donor age, anhepatic phase duration, and pre-incision blood glucose independently predict postoperative SIH. This simplified predictive model provides clinicians a practical tool for early identification and targeted management of high-risk patients to mitigate hyperglycemia-related complications.
BACKGROUND Pancreatoblastoma is a rare malignant epithelial tumor of the pancreas, predominantly affecting children. However, the prognosis is significantly poorer in adults, who typically present with liver metastasis. The management of adult pancreatoblastoma with liver metastases poses a significant challenge, and the median survival remains poor. CASE SUMMARY A 49-year-old male was incidentally found to have a pancreatic body/tail mass and liver metastasis during routine health screening. He underwent distal pancreatectomy, splenectomy, and hepatectomy, with pathology confirming pancreatoblastoma. Over a 7-year follow-up, the patient experienced multiple liver recurrences, managed with repeated resections, systemic chemotherapy, targeted therapy with surufatinib, transarterial chemoembolization, and internal radiation therapy following detection of fibroblast growth factor receptor 1-synaptonemal complex protein 1 gene rearrangement. Serial 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging played a crucial role in detecting recurrence and monitoring treatment response. The patient survived 87 months from initial diagnosis, significantly exceeding the reported median survival. CONCLUSION This case outlines the positron emission tomography/computed tomography presentation of and therapeutic strategies for pancreatoblastoma with liver metastases.
Viruses are diverse and functionally significant members of the soil community, but how they respond to climate warming remains underexplored, especially in deeper soil layers. Here, we utilized a whole-soil-profile warming experiment (similar to 4 degrees C above ambient across the top 1 m of soil) in an alpine grassland to investigate how warming influences soil viral diversity and potential activity across different soil depths. Through the integration of short- and long-read metagenomics with viromics, we discovered numerous novel viruses. Additionally, our findings revealed that after 5 years of warming, viral diversity decreased in surface soils but increased in deeper soils, mirroring but accentuating changes in host diversity. Warming increased the relative abundance of virulent viruses, possibly due to the alleviation of nutrient limitations. This study revealed the depth-dependent responses of soil viruses to climate warming, suggesting that deeper soils may become hotspots for viral diversity and activity under warming scenarios.
Biliary stricture, primarily caused by inflammation, hepatobiliary and pancreatic malignancies and other pathological factors, often leads to impaired bile drainage and subsequent poor clinical outcomes. While biliary stent implantation has become a standard palliative and therapeutic intervention, conventional plastic and metal stents are limited by issues such as biofilm formation, epithelial hyperplasia, and the necessity for secondary removal surgery. The emergence of biodegradable stents offers a promising alternative by providing temporary mechanical support and controlled in vivo degradation, thereby eliminating the need for retrieval procedures. However, single-material stents often fail to address the complex and varied clinical demands, particularly in cases involving biliary fibrosis, infection, or malignancy. This review comprehensively summarizes recent advances in functionalized biodegradable biliary stents, referring to additional capabilities beyond their primary mechanical function, with a focus on material innovations and their enhanced functionalities such as anti-fibrotic, anti-tumor, antimicrobial, anti-corrosion, and visualizable properties. We also discuss integrated therapeutic strategies, such as drug-eluting systems and tissue-engineered scaffolds, alongside manufacturing breakthroughs like 3D printing. Furthermore, we also highlight the persistent translational challenges and preclinical limitations of current biodegradable stent technologies, while outlining promising directions for future research to bridge the gap between experimental development and clinical application.
Antibiotic resistance poses a significant threat to human health, and wastewater treatment plants (WWTPs) are important reservoirs of antibiotic resistance genes (ARGs). Here, we analyze the antibiotic resistomes of 226 activated sludge samples from 142 WWTPs across six continents, using a consistent pipeline for sample collection, DNA sequencing and analysis. We find that ARGs are diverse and similarly abundant, with a core set of 20 ARGs present in all WWTPs. ARG composition differs across continents and is distinct from that of the human gut and the oceans. ARG composition strongly correlates with bacterial taxonomic composition, with Chloroflexi, Acidobacteria and Deltaproteobacteria being the major carriers. ARG abundance positively correlates with the presence of mobile genetic elements, and 57% of the 1112 recovered high-quality genomes possess putatively mobile ARGs. Resistome variations appear to be driven by a complex combination of stochastic processes and deterministic abiotic factors.
Fungal diversity influences both plant diversity and ecosystem functioning, but how fungi mediate the relationship between plant diversity and ecosystem multifunctionality is not as well understood. To address this knowledge gap, we manipulate plant species richness and soil fungal diversity (via fungicide addition) in 190 experimental plant communities and measure ten ecosystem functions to assess ecosystem multifunctionality. We find that reduced fungal diversity (via fungicide addition) decreases ecosystem multifunctionality, but only in plant communities with low species richness, indicating that soil fungal diversity can buffer the effects of plant diversity loss on ecosystem multifunctionality. Selection effects (i.e., superiority of dominant plant species) and phylogenetic clustering of the fungal community (i.e., functional redundancy) increase with plant species richness when fungicide is added, revealing potential mechanisms through which species-rich plant communities can mitigate the negative effects of reduced fungal diversity and maintain ecosystem multifunctionality. Our study emphasizes the importance of interactions between plant and fungal diversity for ecosystem multifunctionality, and highlights the need to conserve fungal diversity, especially in ecosystems with low plant diversity that are threatened by global change.
BACKGROUND:Calciphylaxis, also called calcific uremic arteriolopathy, is characterized by microvascular calcification and occlusion, which is commonly seen in patients with end-stage renal disease (ESRD). Although several studies have demonstrated an association of calciphylaxis with ESRD, reports linking calciphylaxis to LT (LT) are scarce. This report presents a rare case of calciphylaxis in a patient who underwent LT, leading to microvascular occlusion and hyperbilirubinemia. CASE SUMMARY:A 34-year-old man presented with a 7-day history of jaundice and severe bilateral leg pain. The patient had undergone LT and was put on hemodialysis for one year due to calcineurin inhibitor-induced ESRD. Physical examination revealed jaundice, leathery skin changes, severe muscle pain in both legs, and penile induration. Laboratory tests identified elevated bilirubin levels, gamma-glutamyltransferase, and alkaline phosphatase, while alanine aminotransferase and aspartate aminotransferase concentrations were within normal limits. Computed tomography (CT) revealed extensive calcifications in the subcutaneous tissue. Three-dimensional CT reconstruction indicated significantly reduced blood flow in the hepatic artery, primarily in the small to medium-sized branches. Contrast-enhanced ultrasonography confirmed hepatic ischemia, with no enhancement seen in hepatic artery branches. Liver biopsy specimen revealed no signs of rejection. The patient decided to receive conservative treatment and succumbed to the illness after six months. CONCLUSION:This case indicates that calciphylaxis should be suspected in patients who have undergone LT with ESRD presenting with hyperbilirubinemia and skin lesions.
Hepatic fibrosis is a progressive liver disease characterized by excessive accumulation of extracellular matrix (ECM) proteins, primarily collagen, in response to chronic liver injury. Despite the availability of treatment options, current therapies face significant challenges, including poor drug targeting and systemic toxicity. In this study, we developed a nanodrug delivery system, Rosiglitazone (RGZ)-loaded perfluoropropane (PFP)-based lipid nanoparticles (LNPs) functionalized with Arg-Gly-Asp (RGD) peptides (RGZ/PFP@LNP-RGD), for ultrasound-assisted targeted therapy of liver fibrosis. RGZ, a selective PPARγ agonist, was encapsulated in LNPs functionalized with RGD peptides, allowing for targeted delivery to activated hepatic stellate cells (aHSCs), the central cells involved in fibrosis progression. PFP, incorporated into the nanoparticle core, serves as an ultrasound-responsive agent, enabling controlled drug release upon ultrasound irradiation. In vitro, RGZ/PFP@LNP-RGD treatment led to a reduction in the expression of key fibrosis markers such as Col Iα1, α-SMA, and TGF-β1 at both the protein and mRNA levels. Ultrasound treatment further enhanced RGZ release from the nanocarriers, improving the inhibition of HSC activation. In vivo, RGZ/PFP@LNP-RGD combined with ultrasound treatment resulted in a marked reduction in liver fibrosis and improved liver function compared to free RGZ treatment. Histological and biochemical assessments confirmed reduced fibrosis marker expression and liver damage. These results suggest that RGZ/PFP@LNP-RGD, especially when combined with ultrasound, offers a promising noninvasive therapeutic strategy for liver fibrosis, with enhanced targeting, controlled drug release, and reduced systemic toxicity.
Polycystic liver disease is a hereditary disease, which is characterized by the presence of multiple cysts within the liver. In this case, we report a patient with multiple cysts in the kidneys and liver, who underwent kidney transplantation in 2019 and then liver transplantation 4 years later. The complexities of performing liver transplantation in a patient with a prior kidney transplant were significant, particularly due to the enlarged liver obscuring critical vascular structures and necessitating careful intraoperative strategies, such as the side-to-side anastomosis or piggyback techniques to ensure venous return and protect the renal graft. One year post-transplant, the patient exhibited stable liver and kidney functions, demonstrating the feasibility of liver transplantation after kidney transplantation from different donor grafts. The surgical technique and perioperative management require careful consideration.
Unravelling biosphere feedback mechanisms is crucial for predicting the impacts of global warming. Soil priming, an effect of fresh plant-derived carbon (C) on native soil organic carbon (SOC) decomposition, is a key feedback mechanism that could release large amounts of soil C into the atmosphere. However, the impacts of climate warming on soil priming remain elusive. Here, we show that experimental warming accelerates soil priming by 12.7% in a temperate grassland. Warming alters bacterial communities, with 38% of unique active phylotypes detected under warming. The functional genes essential for soil C decomposition are also stimulated, which could be linked to priming effects. We incorporate lab-derived information into an ecosystem model showing that model parameter uncertainty can be reduced by 32–37%. Model simulations from 2010 to 2016 indicate an increase in soil C decomposition under warming, with a 9.1% rise in priming-induced CO 2 emissions. If our findings can be generalized to other ecosystems over an extended period of time, soil priming could play an important role in terrestrial C cycle feedbacks and climate change.
Abstract Background Muscular dystrophies (MD) are a group of genetically inherited disorders characterized by progressive muscle degeneration. Prior observational studies have indicated potential, yet inconclusive, links between MD and liver conditions such as non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Despite these associations, a definitive causal relationship between MD and NAFLD has not been firmly established. Objective Our objective was to assess the potential causal relationships between of MD and liver conditions such as NAFLD and/or NASH, using the latest data available. Methods We employed a two-sample Mendelian Randomization (MR) approach, drawing on genome-wide association study (GWAS) summary statistics for MD and NAFLD/NASH. Furthermore, we performed sensitivity analyses to ensure the reliability and robustness of our findings. Results Our findings did not reveal any significant evidence supporting a causal link between MD and NAFLD (NSNP = 8, odds ratio [OR]: 0.986, 95% CI: 0. 931-1.043, P = 0.62) or NASH (NSNP = 8, odds ratio [OR]: 0.859, 95% CI: 0.692–1.066, P = 0.17). The statistical analysis indicated that the causality between MD and NAFLD/NASH was not significant (P > 0.05). Furthermore, our sensitivity analysis did not identify any significant heterogeneity or instances of horizontal pleiotropy. Conclusions The study concludes that there is no substantial evidence to suggest a causal relationship between MD and NAFLD/NASH. This finding could lead to a reevaluation of the necessity for extensive and potentially costly liver investigations in MD patients. It also suggests that other confounding factors might be at play in the previously observed associations, highlighting the need for further research in this area.
Disentangling the assembly mechanisms controlling community composition, structure, distribution, functions, and dynamics is a central issue in ecology. Although various approaches have been proposed to examine community assembly mechanisms, quantitative characterization is challenging, particularly in microbial ecology. Here, we present a novel approach for quantitatively delineating community assembly mechanisms by combining the consumer-resource model with a neutral model in stochastic differential equations. Using time-series data from anaerobic bioreactors that target microbial 16S rRNA genes, we tested the applicability of three ecological models: the consumer-resource model, the neutral model, and the combined model. Our results revealed that model performances varied substantially as a function of population abundance and/or process conditions. The combined model performed best for abundant taxa in the treatment bioreactors where process conditions were manipulated. In contrast, the neutral model showed the best performance for rare taxa. Our analysis further indicated that immigration rates decreased with taxa abundance and competitions between taxa were strongly correlated with phylogeny, but within a certain phylogenetic distance only. The determinism underlying taxa and community dynamics were quantitatively assessed, showing greater determinism in the treatment bioreactors that aligned with the subsequent abnormal system functioning. Given its mechanistic basis, the framework developed here is expected to be potentially applicable beyond microbial ecology.
Understanding the temporal succession of ecological communities and the underlying mechanisms in response to climate warming is critical for future climate projections. However, despite its fundamental importance in ecology and evolution, little is known about how the Archaea domain responds to warming. Here we showed that experimental warming of a tallgrass prairie ecosystem significantly altered the community structure of soil archaea and reduced their taxonomic and phylogenetic diversity. In contrast to previous observations in bacteria and fungi, we showed convergent succession of the soil archaeal community between warming and control. Although stochastic processes dominated the archaeal community, their relative importance decreased over time. Furthermore, the warming-induced changes in the archaeal community and soil chemistry had significant impacts on ecosystem functioning. Our results imply that, although the detrimental effects of biodiversity loss on ecosystems could be much severer, the soil archaeal community structure would be more predictable in a warmer world.
Background & Aims: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes.Methods: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI. Results: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to - 1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference - 11.66; 95% CI -21.81 to -1.51; p = 0.025).Conclusions: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach.Clinical trial registration: chictr.org. ChiCTR1900021158.